Uganda: Why ‘we’re in it for the long haul’

It’s a long way to go to study cancer, but within the East African nation of more than 30 million people the Hutchinson Center is gaining knowledge, saving lives

Oct. 27, 2009

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By Brad Broberg

Dr. Jackson Orem, head of the Uganda Cancer Institute and Dr. Larry Corey, co-director of the Vaccine and Infectious Diseases Institute tour the UCI facilities. Their collaboration, which began in the mid-90's, was focused on studying human herpesvirus.

Photo by Erica Sessle

The Fred Hutchinson Cancer Research Center has received a $500,000 grant from the United States Agency for International Development to aid in the construction of the first American-sponsored cancer clinic and medical-training facility in Africa. (Link to Associated Press coverage.) The facility will be built on the campus of the Uganda Cancer Institute in Kampala, Uganda. This is the story of how the Hutchinson Center got there and why the collaboration with the Uganda Cancer Institute matters.

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When Dr. Corey Casper joined the Hutchinson Center nine years ago, the Center’s commitment to HIV/AIDS research puzzled him.

“It was an engima to me why a cancer center would have a premier HIV/AIDS program,” Casper said.

The reason is simple. The Hutchinson Center has been studying infectious disease since day one, when fighting infections was a vital part of the Center’s pioneering use of bone marrow transplants to treat leukemia.

In the beginning it was all about supporting the transplant program, but over time the Center’s infectious-disease agenda evolved, pointing investigators down new paths.

It led the Center to run the largest test program of HIV vaccines in the world—the HIV Vaccine Trials Network—and to establish a Vaccine and Infectious Disease Institute. Now, the growing focus on viruses, bacteria and parasites as causes of cancer is inspiring the Center to collaborate with a poor but determined population on the other side of the globe.

MOU solidifies partnership

The partnership between the Hutchinson Center and the Uganda Cancer Institute began with a pilot study in 2004 and solidified in April 2008 with the signing of a memorandum of understanding. The five-year agreement will capitalize on the combined strength of the Center’s cancer and infectious disease programs to better prevent, detect and treat infection-related cancers in Uganda and throughout the world.

“It puts us at the intersection of cancer and infectious disease just as momentum to explore their connection is growing,” Casper said. “No one is better suited to work on this than we are.”

Casper, an investigator with VIDI, is co-director of the new Uganda Program on Cancer and Infectious Diseases (UPCID). Joining him as co-director is Dr. Jackson Orem, head of UCI. By making a commitment in Uganda, the Hutchinson Center joins organizations such as the University of Washington, the Bill and Melinda Gates Foundation and PATH (Program for Appropriate Technology in Health) that are putting Seattle at the forefront of global health.

Uganda is a long way to go to study cancer. But the distance—8,800 miles—is offset by a unique set of conditions that make the East African nation one of the most productive places in the world to investigate infection-related cancers—and a place where the Center can directly help save thousands of lives. Through UPCID, Center and Ugandan researchers can work with a unique population where six out of 10 of the most common cancers are caused by infectious disease; they can study the etiology biology, treatment and prevention of these infection-associated cancers.

“In Uganda, cancer is overshadowed by communicable diseases and hence not accorded high priority,” Orem said. “But that doesn’t mean that cancer is rare. Instead, it is growing due to many factors including the aging population, infections and probably environmental changes.”

Although the public doesn’t typically associate cancer with infectious disease, between 20 percent and 25 percent of all cancers—including liver, cervical and gastric cancer—are caused by viruses and bacteria. Each year, 1.5 million people throughout the world die from infection-related cancers.

A chemotherapy suite at the Uganda Cancer Institute.

Two such cancers—Kaposi sarcoma and Burkitt lymphoma—are especially hitting hard Uganda’s 30 million people. Yet the country has only one cancer treatment facility of modest means—UCI—and, when the Center began its involvement, there was only one oncologist caring for more than 10,000 patients a year.

This gives UPCID two huge opportunities:

To train more Ugandan doctors as oncologists

To conduct studies that would be difficult to pursue in the U.S., where Kaposi sarcoma and Burkitt lymphoma are far less common.

“What the collaboration means is that we have a starting point to expand research and help young people in Uganda see a future in oncology,” Orem said.

Similar opportunities exist in other East African countries. What sets Uganda apart is its long history of education and medical research.
Background: The Uganda Cancer Institute

A former British colony, Uganda is home to Makerere University, one of Africa’s oldest and most prestigious universities, and Mulago Hospital, which supports the university’s medical school and hosts UCI. Another plus: Uganda has maintained a registry of cancer patients—certified by the World Health Organization—since 1954. “That’s really important if you want to do any sort of population-based study,” Casper said.

A milestone in cancer research occurred in Uganda in 1958 when Dr. Dennis Burkitt, an Irish surgeon, described a childhood tumor that would become known as Burkitt lymphoma. Uganda made history again a decade later when UCI pioneered the use of combination chemotherapy to treat Burkitt lymphoma—a method that is now standard treatment for many cancers.

Over the years, UCI has published more than 200 studies and compiled a long history of working with international partners such as the U.S. National Cancer Institute, which helped found UCI in 1967. “There’s a lot of political support for collaboration in Uganda,” said Erica Sessle, managing director of UPCID. “There are so many great people working both in Uganda and here at the FHCRC.”

The potential to make meaningful progress in Uganda has already been demonstrated. Working with international partners, the country has cut the prevalence of HIV in the population from 41 percent in the 1980s to 6 percent today. UPCID’s goal is to make similar inroads against infection-related cancers—and apply what is learned in Uganda in the U.S. and the rest of the world.

Researchers hope to answer a number of key questions:

How are cancer-causing infections transmitted and acquired?

What factors govern the progression from chronic infection to cancer?

Can the progression to cancer be predicted?

Which therapies can be employed to prevent infection-related cancers?

The Ugandan Ministry of Health has pledged $1.8 million to renovate and repurpose the existing buildings of Uganda Cancer Institute.

Photo by Rob Gipman

The genesis of the Center’s collaboration in Uganda was the Center’s focus on human herpesvirus (HHV), which began in the mid-1990s under Dr. Larry Corey, co-director of VIDI. Later, the opportunity to study how one particular herpesvirus, HHV8, causes Kaposi sarcoma, brought Casper to the Center.

At the time, Kaposi sarcoma was occurring at an epidemic rate among AIDS patients, whose weakened immune systems made it easier for the virus to gain a foothold. However, as AIDS treatment improved, the rate of Kaposi sarcoma in the U.S. subsided—good news, but also a problem.

While it was still easy to find people carrying the HHV8 virus, it became hard to find people who developed cancer from the virus, stymieing efforts to study the disease’s progression. Casper needed a population with high rates of both HHV8 and Kaposi sarcoma, which causes tumors of the skin and potentially internal organs, to continue his research.

Uganda, where Kaposi sarcoma occurs at a high rate independent of AIDS, fit the bill. After Casper and Corey made separate trips to the country, they secured an Early Detection Initiative grant from the Center to conduct a pilot study through UCI.

UCI pilot study

In Uganda, 84 percent of the population is infected with the HHV8 virus. The 120-person study looked at why some people are able to keep the virus in check while others develop Kaposi sarcoma. The answer could help predict and prevent Kaposi sarcoma as well as offer insights about other infection-related cancers.

The study called for 120 participants to collect daily samples of their saliva for a month and to visit UCI once a week, where blood and tissue samples were taken. The study was housed in a pair of rooms that lacked both electricity and running water.

“It would be an ambitious study to do even in Seattle,” Casper said. “There were people who said it couldn’t be done.”

Led by Casper, the study enrolled all 120 participants within two months and achieved a 97 percent rate of compliance with study protocols. Although the study represents only a small first step toward any definitive findings, it signaled that high-level research could be carried out in Uganda.

“The pilot was essentially a feasibility study and its success opened the door for additional collaborations involving other investigators at the Center,” Casper said.

By formalizing the relationship between UCI and the Hutchinson Center, UPCID will sustain the momentum built over the last four-plus years. “We’re not in this to collect data and then leave,” Corey said. “We’re in it for the long haul.”

Opportunities for investigators

The needs and opportunities in Uganda are drawing interest from investigators throughout the Hutchinson Center, including Dr. Alan Kristal from the Public Health Sciences Division.

In Uganda, far fewer people with Kaposi sarcoma respond to treatment than would be expected. Many are also underweight. Kristal, who specializes in the connection between diet and cancer, is leading a trial with Casper to learn whether providing nutritional supplements will improve treatment success.

Their trial illustrates the two-way nature of the Center’s mission in Uganda. “The biggest building block in a situation like this is trust,” Corey said. “We want to do research and the Ugandans want to know that our research will benefit their country.”

One of the biggest benefits the Center is bringing to Uganda is a training program to address the country’s dearth of oncologists. “It’s pretty overwhelming what they face over there,” Casper said. “We looked at that and said we have to do something about it.”

Internship program for medical professionals

During the past two years, the program has tripled the number of oncologists in Uganda. Joining Orem, longtime director of UCI, is Dr. Victoria Walusansa, who spent a year studying oncology in Seattle. Then came Dr. Amos Mwaka.

The plan is to train five more Ugandan doctors over the next three years. “Eventually, we hope to expand the program to include other medical professionals such as nurses and pharmacologists,” Casper said.

The burden of cancer in Uganda is high. The number of people who are diagnosed with cancer every year approximates the number of cancer deaths. Much of the poor prognosis is explained by limited opportunities for early detection and treatment due to a lack of human and financial resources.

Burkitt lymphoma is the most common form of childhood cancer in Central Africa.

Photo by Rob Gipman

Burkitt lymphoma, which is associated with Epstein-Barr virus, is an example of a highly treatable disease that continues to claim lives in Uganda. Rare in the U.S, the disease is the most common form of childhood cancer in Central Africa.

Frequently characterized by massive swelling of the jaw, Burkitt lymphoma is a rapidly growing tumor that doubles in size every 24 hours. The tumor’s explosive growth is one reason the National Cancer Institute helped found UCI because it enabled researchers to see results from potential cancer treatments very quickly.

Since the tumor grows so fast, early detection and treatment is critical. However, most Ugandan cancer patients don’t find their way to UCI until they are in the late stages of illness. They often consult a traditional healer before going to a local doctor, who may or may not be able to make a timely diagnosis. It all adds up to dangerous delays in reaching UCI—if they make it at all.

Located in the capital city of Kampala, UCI is a long trek from the rural villages where many Ugandans live. Although treatment may cost only a few hundred dollars, that’s a fortune in Uganda. Plus families are responsible for providing all nonmedical care for patients, including food.

With each collaboration between the Hutchinson Center and UCI have come modest upgrades to UCI’s capabilities through additional staff, supplies and equipment. But there are limits to what can be accomplished in the outdated and overcrowded facility.

Creating a 'center of excellence'

One of UPCID’s goals is to raise $3 million for a new building to house modern research, patient care and education programs and services. “It’s all very much in the beginning stages, but what we’re hoping to do is create a center of excellence in infection-related cancer,” Sessle said.

Such a facility would expand access to care for the Ugandan people. At the same time, it would expand opportunities here at home. The Center plans to send up to 20 faculty members to Uganda in the next five years to train Ugandan clinicians and scientists in a wide variety of subjects and to work collaboratively on research projects.

“My hope,” Corey said, “is that we establish a first-class facility in Uganda, train a significant number of Ugandan oncologists and that people who are interested in international oncology will come to the Center for the chance to work in Uganda.”